P11 COMBINED DIFFUSION WEIGHTED WHOLE BODY MRI (DW-MRI) AND MULTIPARAMETRIC FLOW CYTOMETRY (MFC) EVALUATION FOR MINIMAL RESIDUAL DISEASE DETECTION IN MULTIPLE MYELOMA PATIENTS: CONCORDANCE ANALYSIS OF THE TWO TECHNIQUES AND PREDICTIVE ROLE AFTER TRANSPLANT
Authors: A. Belotti, R. Ribolla, C. Crippa, M. Chiarini, V. Giustini, S. Ferrari, A. Peli, C. Cattaneo, A. Roccaro, B. Frittoli, L. Grazioli, G. Rossi, A. Tucci
Journal: HemaSphere (2023)

Introduction: The increasing availability of functional imaging techniques has enabled the combined evaluation of MRD in MM within and outside bone marrow (BM). Diffusion-weighted whole-body MRI (DW-MRI) is increasingly used in the management of MM patients (pts) and criteria for Response Assessment Category (RAC) have been established by the Myeloma Response Assessment and Diagnosis System (MY-RADS), with a 5 point scale defining complete imaging response (i.e. RAC 1) or residual-progressive disease after treatment (i.e. RAC 2-5). We compared the results of MY-RADS with those of MRD assessment by flow cytometry (MFC) at different timepoints after autologous stem cell transplant (ASCT) in order to evaluate the agreement of the two techniques and to investigate the predictive role of a dual assessment of response on patients outcome. Methods: we retrospectively assessed MRD in transplant eligible MM pts by performing combined evaluations of BM and DW-MRI at day +100 after ASCT and yearly thereafter. MY-RADS RAC criteria were applied for the evaluation of imaging residual disease, whereas 8-color MFC (sensitivity 10-5) was performed for BM MRD detection. The concordance between DW-MRI and MFC results was calculated and the level of agreement was expressed by Cohen’s kappa statistics. The outcome according to the combined DW-MRI/MFC evaluation after ASCT was also investigated. Results: from 2016 to 2021 we performed 143 combined evaluations of DW-MRI and MFC in 79 pts. MFC was negative in 96 BM samples (67%); according to MY-RADS, a complete imaging response (RAC1) was observed in 107 cases (75%), whereas some residual disease was identified in 36 cases (25%) [RAC2: 24 (17%), RAC3: 6 (4%), RAC4: 3 (2%), RAC 5: 3 (2%) respectively]. The concordance between WB-MRI and BM MFC results was low (68.5%, kappa 0,067: 13% both positive, 55% both negative). MRD assessment at day +100 after ASCT (considering the second ASCT in case of double transplant) was available in 76 patients [27(35%) ISS-3, 29 (38%) high risk cytogenetics]. Pts were treated with the following induction regimens: VTD 56 (74%), DaraVCD 6 (8%), DaraVRD 6 (8%), VRD 6 (8%), KCD 1 (1%), KRD 1 (1%); 37 pts (49%) received double ASCT (MEL200). Response rates were sCR 25%, CR 45%, VGPR 21%, PR 9%. MFC was negative in 48 samples (63%), whereas RAC1 was observed in 52 (68%) pts. Seventy pts (92%) received maintenance therapy with lenalidomide (58), daratumumab-lenalidomide (6), daratumumab-ixazomib (6). After a median follow up of 42 months, PFS was significantly better for patients with DW-MRI RAC1 and MFC negative after ASCT, compared to pts with RAC ≥2 and MFC positive results (PFS NR vs 22.3 months; p <0.0001, HR 0.10 - 95%CI: 0,02-0,43). Intermediate PFS was observed for pts with either imaging or BM positive results (PFS NR), with a significantly different outcome of the three subgroups (p <0.0001). A trend of different OS was also observed, although not statistically significant (3y OS: 95% for double negative pts, 89% for pts with either imaging or BM positive results, 60% for double positive pts, p 0.06). Conclusion: DW-MRI is a powerful tool to evaluate the prognosis of pts treated with ASCT; the low concordance between DW-MRI and MFC highlights the complementarity of the two techniques for the definition and monitoring of response in order to better refine the prognosis of pts achieving CR after ASCT